The principal goals of this research project are to determine the kinetic basis for the decrease in growth rate of neoplastic or normal cell populations as the cell density increases; to develop new methods by which kinetic changes induced by drug treatment can be monitored in vitro or in vivo; and to investigate in detail the cell cycle specificity of certain drugs used in cancer chemotherapy, including synergistic or antagonistic interactions between different drugs. Relevant to all of these studies is the concept of a resting cell component which may be present in advanced leukemia or other diseases. Such cells are normally resistant to the cytotoxic effects of cycle-specific drugs, but can apparently resume active proliferation during remission, eventually leading to relapse. If they could be stimulated to reenter the cycle in synchrony, it might then be possible to kill them with appropriate phase-specific agents. The proposed studies will investigate these and related questions, utilizing tracer methods and rapid flow microfluorometry to determine the response of synchronized or asynchronous cells in different growth phases to selected drugs. BIBLIOGRAPHIC REFERENCES: Fried, J., Arlin, Z., and Clarkson, B. Flow microfluorometry of bone marrow cells from a patient with acute lymphocytic leukemia during chemotherapy. In: "Proceedings of the Second International Symposium on Pulse Cytophotometry (J. Schumann, W. Gohde, and Th. Buchner, eds), European Press, Ghent, Belgium, (in press, 1976). Fried, J., Arlin, Z., Arlikpala, A., Tan, C.T.C., and Clarkson, B.: Kinetic response of human leukemic and lymphoma cells in vivo to combination chemotherapy using flow microfluorometry. Cancer Chemotherapy Reports (in press, 1976).